Insulin and the gastrointestinal tract

• Published in: Journal of controlled release Vol. 46; no. 1-2; pp. 89 - 98
• Main Authors: Saffran, Murray, Pansky, Ben, Budd, G.Colin, Williams, Frederick E
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier B.V 05.05.1997; Elsevier
• Subjects: Biological and medical sciences; Colon; Dogs; General pharmacology; GI insulin; Hormones. Endocrine system; Medical sciences; Oral insulin; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Rats; Oral insulin; Rats; GI insulin; Colon; Dogs; Pancreatic hormone; Rat; Drug carrier; Proteins; Protein hormone; Hypoglycemic agent; Azo polymer; Dog; Fissipedia; Carnivora; Pharmaceutical technology; Digestive system; Control release polymer; Rodentia; Gut; Oral administration; Capsule; Permeability; Insulin; Vertebrata; Mammalia; Animal; Dosage form; Absorption enhancer
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(96)01578-7

To provide a less cumbersome and more socially accepted form of insulin treatment than subcutaneous injections, we have designed an azopolymer system to deliver insulin with an absorption enhancer to the upper colon. In pancreatectomized dogs repeated oral doses of insulin in azopolymer-coated capsules lower the diabetic hyperglycemia to near normal values. Direct visualization of capsules containing radionuclides and coated with two new batches of azopolymer demonstrated that the capsules either passed intact through the gut or were opened in the small intestine. Direct visualization and insulin delivery using the same azopolymer will be necessary to locate the site of insulin delivery, but there remains the possibility that the insulin was delivered within the small intestine. To understand the effect of large doses of insulin delivered to the upper GI tract, an insulin solution was substituted for the drinking water of normal and diabetic rats. This produced temporary decreases in blood glucose levels, showing that in rats some absorption of insulin takes place above the colon. However, these rats became hyperphagic and lost weight. On post mortem examination the gut was distended with undigested food. Insulin seemed to inhibit processing of the food by the gut, in confirmation of observations by Elliasson and coworkers in human volunteers. The inhibitory effect of insulin on the gut, coupled with the presence of insulin receptors on the mucosal side of the gut and the presence of other pancreatic peptides in the gut, suggested to us that the gut may be able to make insulin. Accordingly, we looked for and found immunocytochemical evidence for preformed insulin in crypt cells in the colon and stomach, as well as the mRNAs for both rat insulins in similar cells. Gut insulin may be involved in the response of the gastrointestinal tract to food. Caution must be exerted in the introduction of high concentrations of insulin into the gastrointestinal tract. The same may be true of other powerful natural agents for which an oral delivery system would be desirable.